Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis.

BACKGROUND: The dynamic interaction between cancer cells and tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is an active barrier to the effector arm of the antitumour immune response. Cancer-secreted exosomes are emerging mediators of this cancer-stromal cross-talk in the TME; however, the mechanisms underlying this interaction remain unclear. METHODS: Exosomes were isolated with ExoQuick exosome precipitation solution. The polarizing effect of TAMs was evaluated by flow cytometry, western blot analysis, immunofluorescence staining and in vitro phagocytosis assays. Clinical cervical cancer specimens and an in vivo xenograft model were also employed. RESULTS: Our previous study showed that hypoxia increased the expression of ZEB1 in cervical squamous cell carcinoma (CSCC) cells, which resulted in increased infiltration of TAMs. Here, we found that hypoxia-induced ZEB1 expression is closely correlated with CD47-SIRPα axis activity in CSCC, which enables cancer cells to evade phagocytosis by macrophages and promotes tumour progression. ZEB1 was found to directly activate the transcription of the CD47 gene in hypoxic CSCC cells. We further showed that endogenous ZEB1 was characteristically enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes to promote SIRPα+ TAM polarization. Intriguingly, exosomal ZEB1 retained transcriptional activity and reprogrammed SIRPα+ TAMs via activation of the STAT3 signalling pathway in vitro and in vivo. STAT3 inhibition reduced the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increased the phagocytosis of CSCC cells by macrophages via decreasing CD47 and SIRPα expression. CONCLUSIONS: Our results suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPα axis. ZEB1-targeted therapy in combination with CD47-SIRPα checkpoint immunotherapy may improve the outcomes of CSCC patients in part by disinhibiting innate immunity.

The Role and Mechanism of MiR-451 in Multidrug Resistance of Leukemia Cell Line K562/A02 / 中国实验血液学杂志

OBJECTIVE@#To detect the differential expressions of miR-451, ABCB1 and ABCC2 in drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, and explore the regulatory relationship between miR-451 and the expressions of ABCB1 and ABCC2 , and the mechanism of miR-451 involved in drug resistance in leukemia.@*METHODS@#CCK-8 assay was used to detect the drug resistance of K562/A02 and K562 cells. Quantitative Real-time PCR (qRT-PCR) was used to verify the differential expressions of miR-451 in K562 and K562/A02 cells. MiR-451 mimic and negative control (miR-NC), miR-451 inhibitor and negative control (miR-inNC) were transfected into K562 and K562/A02 cells respectively, then qRT-PCR and Western blot were used to detect the expression levels of mRNA and protein of ABCB1 and ABCC2 in K562 and K562/A02 cells and the transfected groups.@*RESULTS@#The drug resistance of K562/A02 cells to adriamycin was 177 times higher than that of its parent cell line K562. Compared with K562 cells, the expression of miR-451 in K562/A02 cells was significantly higher (P <0.001), and the mRNA and protein expression levels of ABCB1 and ABCC2 in K562/A02 cells were significantly higher than those in K562 cells (P <0.001). After transfected with miR-451 inhibitor, the expression of miR-451 was significantly down-regulated in K562/A02 cells (P <0.001), the sensitivity to chemotherapy drugs was significantly enhanced (P <0.05), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly decreased (P <0.01). After transfected with miR-451 mimic, the expression of miR-451 was significantly upregulated in K562 cells (P <0.001), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly increased (P <0.01).@*CONCLUSION@#There are significant differences in the expressions of miR-451, ABCB1 and ABCC2 between the drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, which suggests that miR-451 may affect the drug resistance of leukemia cells by regulating the expression of ABCB1 and ABCC2.

Imatinib inhibits pericyte-fibroblast transition and inflammation and promotes axon regeneration by blocking the PDGF-BB/PDGFRß pathway in spinal cord injury.

BACKGROUND: Fibrotic scar formation and inflammation are characteristic pathologies of spinal cord injury (SCI) in the injured core, which has been widely regarded as the main barrier to axonal regeneration resulting in permanent functional recovery failure. Pericytes were shown to be the main source of fibroblasts that form fibrotic scar. However, the mechanism of pericyte-fibroblast transition after SCI remains elusive. METHODS: Fibrotic scarring and microvessels were assessed using immunofluorescence staining after establishing a crush SCI model. To study the process of pericyte-fibroblast transition, we analyzed pericyte marker and fibroblast marker expression using immunofluorescence. The distribution and cellular origin of platelet-derived growth factor (PDGF)-BB were examined with immunofluorescence. Pericyte-fibroblast transition was detected with immunohistochemistry and Western blot assays after PDGF-BB knockdown and blocking PDGF-BB/PDGFRß signaling in vitro. Intrathecal injection of imatinib was used to selectively inhibit PDGF-BB/PDGFRß signaling. The Basso mouse scale score and footprint analysis were performed to assess functional recovery. Subsequently, axonal regeneration, fibrotic scarring, fibroblast population, proliferation and apoptosis of PDGFRß+ cells, microvessel leakage, and the inflammatory response were assessed with immunofluorescence. RESULTS: PDGFRß+ pericytes detached from the blood vessel wall and transitioned into fibroblasts to form fibrotic scar after SCI. PDGF-BB was mainly distributed in the periphery of the injured core, and microvascular endothelial cells were one of the sources of PDGF-BB in the acute phase. Microvascular endothelial cells induced pericyte-fibroblast transition through the PDGF-BB/PDGFRß signaling pathway in vitro. Pharmacologically blocking the PDGF-BB/PDGFRß pathway promoted motor function recovery and axonal regeneration and inhibited fibrotic scar formation. After fibrotic scar formation, blocking the PDGFRß receptor inhibited proliferation and promoted apoptosis of PDGFRß+ cells. Imatinib did not alter pericyte coverage on microvessels, while microvessel leakage and inflammation were significantly decreased after imatinib treatment. CONCLUSIONS: We reveal that the crosstalk between microvascular endothelial cells and pericytes promotes pericyte-fibroblast transition through the PDGF-BB/PDGFRß signaling pathway. Our finding suggests that blocking the PDGF-BB/PDGFRß signaling pathway with imatinib contributes to functional recovery, fibrotic scarring, and inflammatory attenuation after SCI and provides a potential target for the treatment of SCI.

M1-type microglia can induce astrocytes to deposit chondroitin sulfate proteoglycan after spinal cord injury.

After spinal cord injury (SCI), astrocytes gradually migrate to and surround the lesion, depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar, which limits the spread of inflammation but hinders axon regeneration. Meanwhile, microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype. However, the effect of microglia polarization on astrocytes is unclear. Here, we found that both microglia (CX3CR1+) and astrocytes (GFAP+) gathered at the lesion border at 14 days post-injury (dpi). The microglia accumulated along the inner border of and in direct contact with the astrocytes. M1-type microglia (iNOS+CX3CR1+) were primarily observed at 3 and 7 dpi, while M2-type microglia (Arg1+CX3CR1+) were present at larger numbers at 7 and 14 dpi. Transforming growth factor-ß1 (TGFß1) was highly expressed in M1 microglia in vitro, consistent with strong expression of TGFß1 by microglia in vivo at 3 and 7 dpi, when they primarily exhibited an M1 phenotype. Furthermore, conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro. This effect was eliminated by knocking down sex-determining region Y-box 9 (SOX9) in astrocytes and could not be reversed by treatment with TGFß1. Taken together, our results suggest that microglia undergo M1 polarization and express high levels of TGFß1 at 3 and 7 dpi, and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFß1/SOX9 pathway. The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University, China (approval No. LLSC20160052) on March 1, 2016.

Disaster vulnerability analysis of Macao hospitals based on Kaiser model / 中华医院管理杂志

Objective:To analyze the disaster vulnerability of hospitals in Macao Special Administrative Region to assess the disaster risk objectively, so as to provide reference for Macao hospitals to formulate their emergency plans and improve their emergency response and handling capacity.Methods:From December 2021 to February 2022, 118 medical staff were selected for a questionnaire survey using the method of departmental stratified random sampling from three general hospitals in Macao. At the same time, 7 full-time medical staff and 2 experts in the field of health care were selected for expert consultation. The main content of the questionnaire was the hospital disaster risk assessment based on the Kaiser model, and three-round expert consultation method was used to determine the model indicators. The risk value of each indicator was calculated to analyze the hospital disaster vulnerability.Results:107 valid questionnaires were collected. The top five events in the hospital disaster risk value were typhoon(52.42%), large-scale public health events/epidemic outbreaks(47.55%), strong thunderstorm convective weather(38.68%), extreme temperature(37.31%) and information system failure(33.75%). As ranked by the total risk value, the categories of hospital disasters were natural disasters(35.69%), information security(29.49%), medical technology accidents(29.36%), equipment technology accidents(26.25%), dangerous goods injuries(25.13%) and personnel injuries(19.98%).Conclusions:Macao hospitals are exposed to the highest total risk value in natural disasters, followed by information security. In addition, the risk value of large-scale public health events and epidemic outbreaks of personal injury is also so high as to deserve attention. Macao hospitals should formulate effective emergency response plans according to the risk values of various disasters and the actual situation of each medical department, so as to minimize the losses caused by disasters to both hospitals and patients.

Hypoglycemic Mechanism of Gegen Qinliantang： An Exploration Based on GPR119/cAMP/GLP-1 Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effects of Gegen Qinliantang（GGQL） on the proliferation and apoptosis of intestinal epithelial cells as well as on the expression of cyclic adenosine monophosphate （cAMP）， G protein-coupled receptor 119 （GPR119）， and glucagon-like peptide-1 （GLP-1）， so as to explore its potential hypoglycemic mechanism. MethodTwenty-five Wistar rats were gavaged with GGQL at the dose of 23 g·kg-1 crude drug， twice a day， which meant that 6 mL was administered into each rat per day for preparing the GGQL-containing serum. After seven consecutive times of administration， the intestinal epithelial L （NCI-H716） cells were cultured with different concentrations （1%， 2.5%， 5%， 7.5%， and 10%） of GGQL. The cell proliferation was evaluated using cell counting kit-8 （CCK-8） and the apoptosis by flow cytometry. The GLP-1 and cAMP contents in cell supernatant were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein GLP-1 and GPR119 levels were assayed by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the control group， GGQL significantly reduced the proliferation of NCI-H716 cells（P<0.05）. As the GGQL concentration increased， its inhibitory effect became more obvious. GGQL at each concentration significantly promoted the apoptosis of NCI-H716 cells （P<0.05）. Compared with the control group， GGQL significantly up-regulated the expression of cAMP， GLP-1， and GPR119 （P<0.05）. The results showed that the effect of GGQL was positively correlated with its concentration， and 10% GGQL exhibited the best effect. ConclusionGGQL effectively inhibits the proliferation of NCI-H716 cells and promotes their apoptosis， and it may promote the secretion of GLP-1 by up-regulating the expression of cAMP and GPR119.

Transcranial direct current stimulation treated by multilead brain reflex instrument accelerates neural functional recovery in a rat model of stroke.

PURPOSE: Clinical research suggests that transcranial direct current stimulation (tDCS) at bilateral supraorbital foramen and inferior orbital rim and nose intersections may facilitate rehabilitation after stroke. However, the underlying neurobiological mechanisms of tDCS remain poorly understood, impeding its clinical application. Here, we investigated the effect of tDCS applied after stroke on neural cells. MATERIALS AND METHODS: Middle cerebral arterial occlusion (MCAO) reperfusion was induced in rats. Animals with comparable infarcts were randomly divided into MCAO group and MCAO + tDCS group. Recovery of neurological function was assessed behaviorally by modified neurological severity score (mNSS). Ischemic tissue damage verified histologically by TTC and HE staining. Immunohistochemical staining, real-time qPCR, and western blot were applied to determine the changes of neural cells in ischemic brains. RESULTS: The results reveal that tDCS treated by multilead brain reflex instrument can promote the recovery of neurological function, remarkably reduce cerebral infarct volume, promote brain tissue rehabilitation, and can effectively inhibit astrocytosis and enhance neuronal survival and synaptic function in ischemic brains. CONCULSIONS: Our study suggests that tDCS treated by multilead brain reflex instrument could be prospectively developed into a clinical treatment modality.

Clinical efficacy of adductor canal blockade combined with transcutaneous electrical acupoint stimulation for total knee arthroplasty / 中国骨伤

OBJECTIVE@#To evaluate the efficacy of adductor canal block (ACB) combined with transcutaneous electrical acupoint stimulation (TEAS)for postoperative analgesia and early functional exercise after total knee arthroplasty (TKA).@*METHODS@#A total of 84 patients underwent primary unilateral TKA from January 2019 to August 2020 were selected, including 45 males and 39 females, aged 66-77 (72.8±8.9) years;body mass index (BMI) was for 19-25 (23.6±3.5) kg /m@*RESULTS@#There were no significant differences in VAS of rest pain and activity pain in postoperative 6, 12 h between two groups (@*CONCLUSION@#TEAS combined with ACB has a better postoperative analgesic efficacy than simple ACB, and can promote early functional exercise of patients. It is safe and effective for postoperative analgesia after TKA.

Clinical, pathological and genetic characteristics of 8 patients with distal hereditary motor neuropathy / 北京大学学报(医学版)

OBJECTIVE@#Distal hereditary motor neuropathy (dHMN) comprises a heterogeneous group of inherited disorders associated with neurodegeneration of motor nerves and neurons, mainly charac-terized by progressive atrophy and weakness of distal muscle without clinical or electrophysiological sensory abnormalities. To improve the recognition and diagnosis of the disease, we summarized the clinical manifestations, electrophysiological, pathological, and genetic characteristics in eight patients with dHMN.@*METHODS@#Eight probands from different families diagnosed with dHMN were recruited in this study between June 2018 and April 2019 at Peking University People's Hospital. Eight patients underwent complete neurological examination and standard electrophysiological examinations. The clinical criteria were consistent with the patients presenting with a pure motor neuropathy with no sensory changes on electrophysiology. The detailed clinical symptoms, neurophysiological examinations, pathological features and gene mutations were analyzed retrospectively. Genetic testing was performed on the eight patients using targeted next-generation sequencing panel for inherited neuromuscular disorder and was combined with segregation analysis.@*RESULTS@#The age of onset ranged between 11 and 64 years (median 39.5 years) in our dHMN patients. All the cases showed a slowly progressive disease course, mainly characterized by distal limb muscle weakness and atrophy. The motor nerve conduction revealed decreased compound muscle action potential amplitude and velocity, while the sensory nerve conduction velocities and action potentials were not affected. Needle electromyography indicated neurogenic chronic denervation in all patients. Muscle biopsy performed in two patients demonstrated neurogenic skeletal muscle damage. Sural nerve biopsy was performed in one patient, Semithin sections shows relatively normal density and structure of large myelinated fibers, except very few fibers with thin myelin sheaths, which suggested very mild sensory nerve involvement. Eight different genes known to be associated with dHMN were identified in the patients by next-generation sequencing, pathogenic dHMN mutations were identified in three genes, and the detection rate of confirmed genetic diagnosis of dHMN was 37.5% (3/8). Whereas five variants of uncertain significance (VUS) were identified, among which two novel variants co-segregated the phenotype.@*CONCLUSION@#dHMN is a group of inherited peripheral neuropathies with great clinical and genetic heterogeneity. Next-generation sequencing is widely used to discover pathogenic genes in patients with dHMN, but more than half of the patients still remain genetically unknown.

Effect of 5-aminoimidazole-4-formamide Ribonucleotide Combined with Interferon on Chronic Myeloid Leukemia K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To study the effect of 5-aminoimidazole-4-formamide ribonucleotide (AICAR) combined with interferon (IFN-α-2b) on the proliferation and apoptosis of chronic myeloid leukemia K562 cells, and explore its possible mechanism.@*METHODS@#CCK-8 method was used to detect the inhibition of cell proliferation. Wright Giemsa method was used to stain and cell morphology was observed by light microscopy. FITC Annexin V/PI double staining method was used to analyze the change of apoptosis rate. Immunocytochemistry method was used to detect the expression of wild-type P53 protein.@*RESULTS@#Different concentration of AICAR was inhibitory effect on K562 cells at different time point of action for 24 h, 48 h, and 72 h, and the inhibition was time and dose-dependent (r=0.71, r=0.84). The combination of AICAR and IFN-α-2b could effectively inhibit the proliferation and promote apoptosis of K562 cells. The inhibition rate of K562 cells was (45.26±2.54)%, and the early apoptosis rate was (33.72±0.23)%, which was statistically significantly different from the control group, AICAR or IFN-ɑ-2b alone (P<0.05). The combination of two drugs promoted the expression of wild-type p53 protein.@*CONCLUSION@#AICAR and/or IFN-ɑ-2b can inhibit the cell proliferation and promote the apoptosis of K562 cells. The combination of two drugs shows synergistic antitumor effect, and its mechanism may be related to the promotion of high expression of wild-type p53 protein.

TrkA regulates the regenerative capacity of bone marrow stromal stem cells in nerve grafts.

We previously demonstrated that overexpression of tropomyosin receptor kinase A (TrkA) promotes the survival and Schwann cell-like differentiation of bone marrow stromal stem cells in nerve grafts, thereby enhancing the regeneration and functional recovery of the peripheral nerve. In the present study, we investigated the molecular mechanisms underlying the neuroprotective effects of TrkA in bone marrow stromal stem cells seeded into nerve grafts. Bone marrow stromal stem cells from Sprague-Dawley rats were infected with recombinant lentivirus vector expressing rat TrkA, TrkA-shRNA or the respective control. The cells were then seeded into allogeneic rat acellular nerve allografts for bridging a 1-cm right sciatic nerve defect. Then, 8 weeks after surgery, hematoxylin and eosin staining showed that compared with the control groups, the cells and fibers in the TrkA overexpressing group were more densely and uniformly arranged, whereas they were relatively sparse and arranged in a disordered manner in the TrkA-shRNA group. Western blot assay showed that compared with the control groups, the TrkA overexpressing group had higher expression of the myelin marker, myelin basic protein and the axonal marker neurofilament 200. The TrkA overexpressing group also had higher levels of various signaling molecules, including TrkA, pTrkA (Tyr490), extracellular signal-regulated kinases 1/2 (Erk1/2), pErk1/2 (Thr202/Tyr204), and the anti-apoptotic proteins Bcl-2 and Bcl-xL. In contrast, these proteins were downregulated, while the pro-apoptotic factors Bax and Bad were upregulated, in the TrkA-shRNA group. The levels of the TrkA effectors Akt and pAkt (Ser473) were not different among the groups. These results suggest that TrkA enhances the survival and regenerative capacity of bone marrow stromal stem cells through upregulation of the Erk/Bcl-2 pathway. All procedures were approved by the Animal Ethical and Welfare Committee of Shenzhen University, China in December 2014 (approval No. AEWC-2014-001219).

Comparison of the Biological Functions between Human Bone Marrow Derived CD106 Mesenchymal Stem Cells and CD106 Subgroup / 中国医学科学院学报

Objective To analyze the differences in biological functions between bone marrow(BM)-derived CD106 mesenchymal stem cells(MSCs)and the CD106 subgroup. Methods The MSCs from normal BM were isolated and expanded.The subgroups of CD106 and CD106 MSCs were sorted.The cell proliferation and adhesion functions,chemotactic activities,adipogenic and osteogenic potentials,senescence,and senescence protein 21(p21)were detected.The capacity of translocation into nucleus of nuclear factor-kappa B(NF-κB)when stimulated by tumor necrosis factor(TNF-α)was measured. Results The proliferative ability was higher in CD106 MSCs than that in CD106 MSCs.In 48 hours,the value of optical density(OD)was significantly higher in CD106 MSCs than that in CD106 subgroup(1.004±0.028 0.659±0.023,=3.946,=0.0225).In 72 hours,this phenomenon was even more pronounced(2.574±0.089 1.590±0.074,=11.240,=0.0000).The adhesive capacity of CD106 MSCs was significantly stronger than that of CD106 subgroup(0.648±0.018 0.418±0.023,=7.869,=0.0002).Besides,the metastasis ability of CD106 MSCs were significantly stronger than that of CD106 subgroup(114.500±4.481 71.000±4.435,=6.900,=0.0005).The CD106 MSCs had signifcnatly lower proportions of senescent cells.The expression of aging protein p21 in CD106 MSCs was significantly lower than that in CD106 MSCs [(17.560±1.421)% (45.800±2.569)%,=9.618,=0.0000].Furthermore,there were no visible pigmenting cells after β-galactosidase staining in CD106 MSCs subgroup.However,in CD106 MSCs,some colored green cells were detected.The rate of NF-κB translocation into nucleus after stimulated by TNF-α was significantly higher in CD106 MSCs than CD106 MSCs [(37.780±3.268)% (7.30±1.25)%,=8.713,=0.0001]. Conclusion Bone marrow-derived CD106 MSCs possess more powerful biological functions than CD106 MSCs.

Clinical Effect of Wandaitang on Endometrial Carcinoma After Operation / 中国实验方剂学杂志

Objective:To observe the effect of syndrome differentiation and treatment with Wandaitang on symptoms, quality of life and function of immunologic after operation of endometrial carcinoma (EC), in order to discuss the mechanism of action according to regulation of microenvironment of EC. Method:The 109 patients were divided into control group (54 cases) and observation group (55 cases) by random number table. Patients in control group got radiotherapy and/or chemotherapy according to different stages after operation. Patients in observation group were additionally given syndrome differentiation and treatment with Wandaitang, 1 dose/day. And a course of treatment was 3 months. Before and after treatment, symptoms, sign, functional assessment of cancer therapy-general (FACT-G) were scored. And levels of T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+), natural killer cell (NK), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), insulin-like growth factor-1(IGF-1), interleukin-17 (IL-17) and IL-10 were detected. Result:After treatment, the scores of symptoms, signs and total scores of the patients in the observation group were lower than the control group (PP+, CD4 + and CD4 +/CD8 + in the observation group were higher than those in the control group(PPβ, IGF-1, IL-17 and IL-10 in the observation group were lower than those in the control group. Conclusion:Wandaitang can ameliorate clinical symptoms, improve quality of life of patients and immune function of organism, regulate multiple cytokines, change the tumor microenvironment of endometrial carcinoma.

Efficacy and safety of the Bushen Tiaochong recipe combined with alendronate sodium for the treatment of postmenopausal senile degenerative osteoporosis:study protocol for a randomized controlled trial / 中国组织工程研究

BACKGROUND: Alendronate sodium is a commonly used western medicine for the treatment of osteoporosis, but it has many adverse reactions.The main component of the traditional Chinese medicine,known as the Bushen Tiaochong recipe,is Epimedium brevicornu Maxim. (epimedium).Pharmacological studies have shown that the main active ingredient of Epimedium is icariin.Icariin has an estrogen-like effect, can prevent against bone loss and improve bone strength, and has a definite effect on the treatment of postmenopausal senile degenerative osteoporosis. OBJECTIVE:To testify the hypothesis that the Bushen Tiaochong recipe combined with alendronate sodium will be more effective,as well as safer and more reliable than alendronate sodium alone for the treatment of postmenopausal senile degenerative osteoporosis. METHODS: Two hundred patients with postmenopausal senile degenerative osteoporosis will be randomly assigned to an observation group and a control group. In the control group, patients will be given alendronate sodium tablets 10 mg/d and calcium carbonate D3 chewable tablets 0.6 g/d.In the observation group,patients will receive the same treatment as the control group and the Bushen Tiaochong recipe,simmering,twice per day(once in the morning and once in the evening).The duration of treatment will be 6 months in both groups. The primary outcome measure is the overall efficacy 6 months after treatment in both groups. The secondary outcome measures are Visual Analogue Scale scores for waist and back pain; lumbar spine (L2–4) bone mineral density; serum levels of calcium, phosphorus, alkaline phosphatase, osteocalcin, estradiol, follicle stimulating hormone, luteinizing hormone, interleukin-1, and interleukin-6 before and 6 months after treatment; and incidence of adverse reactions 6 months after treatment. This trial has been approved by the Ethics Committee of the Affiliated Hospital of Qinghai University of China (approval number: QHY1703F). The study protocol will be conducted in accordance with the Declaration of Helsinki,formulated by the World Medical Association.Written informed consent will be obtained from all participants. The recruitment of subjects will begin in January 2018. Samples and data will be collected from January to December 2018. Outcome measures will be analyzed in March 2019. This trial will be completed in April 2019. The results of the trial will be reported in a scientific conference or disseminated in a peer-reviewed journal. This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ONC-17013947). DISCUSSION: We hope to verify that the Bushen Tiaochong recipe combined with alendronate sodium provides better results than alendronate sodium alone for the treatment of postmenopausal senile degenerative osteoporosis.

Effect of EPO on PRDM16, FGF21 expression and STAT phosphorylation of brown adipose tissue in HFD mice / 中国应用生理学杂志

OBJECTIVE@#To investigate the effect of erythropoietin (EPO) on blood glucoseand plasma insulin level, index of insulin resistance (HOMA-IR), introperitoneal glucose tolerance test (IPGTT), the mRNA and protein level of PR domain-containing 16 (PRDM16), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), fibroblast growth factor 21 (FGF21) of brown adipose tissue (BAT) in mice fed with high fat diet (HFD) in order to provide clues for the mechanism of obesity and complication.@*METHODS@#Twenty C57BL/6J male mice fed with HFD were randomly divided into control group (HFD-Con) and EPO group (HFD-EPO), mice in the two groups were injected intraperitoneally normal saline and EPO (200 IU/kg) res pectively, 3 times per week for consecutive 4 weeks.Then the body weight, blood glucose, plasma insulin level, HOMA-IR and IPGTT were detected.The mRNA and protein level of PRDM16, FGF21, p-STAT3/STAT3 in brown adipose tissue were detected by real-time quantitative RT-PCR and Western blot respectively.@*RESULTS@#After intraperitoneal injection of EPO for 4 weeks, the body weight of the mice in HFD-EPO and HFD-Con groups was (26.65±0.85) g and (31.50±1.6 0) g respectively.The blood glucose of the mice in HFD-EPO group[(62.79±8.09) mg/dl]was significantly decreased compared with that in HFD-Con group[(91.06±9.86) mg/dl].The plasmainsulin level in HFD-EPO group[(10.56±1.06)μU/ml]was significantly decreased compared with that in HFD-Con group[(13.2±1.1)μU/ml, < 0.01].The level of IPGTT in HFD-EPO group was significantly ameliorated and th e HOMA-IR decreased compared with those in HFD-Con group.The mRNA and protein expressions of PRDM16, FGF21 and the level of STAT3 of brown adipose tissue in HFD-E PO group were increased obviously.And there was no difference of FGF21 mRNA content in liver and FGF21 content in plasmabetween the two groups.@*CONCLUSIONS@#EPO could promote differentiation of brown adipose tissue by increase in the express ion of PRDM16, and decrease the blood glucose level, ameliorate glucose metabolism in obses mice.

Research on the Innovation of Medical Service Quality Evaluation Under Mobile Internet Environment / 中国医院管理

Objective Under the trend of "lnternet + Medical service",key indicators of medical service quality are developed for innovation of monitoring medical service quality.Methods Converting the perception experience of each service item in the process of seeking medical treatment into quantitative measurement,and creating SERVQUAL service quality evaluation system.Results Based on the "patient experience",framework of medical service quality is constructed.The first level indicators include tangibility,reliability,responsiveness,assurance and care,economy,and effectiveness,etc.,while there are 25 secondary indicators.Conclusion Platforms can be constructed using mobile internet intelligent terminals based on patients' experiences.Medical service quality can be evaluated objectively in a timely manner through them.

Quantitative evaluation of white matter development in fetus with growth restriction by diffusion tensor imaging / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate whether fetal growth restriction (FGR) has an adverse effect on white matter development.</p><p><b>METHODS</b>A total of 28 full-term small for gestational age (SGA) infants were enrolled as study subjects and 15 full-term appropriate for gestational age infants were enrolled as control group. Conventional head magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed for all infants. The white matter was divided into 122 regions. The two groups were compared in terms of fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of different brain regions.</p><p><b>RESULTS</b>Compared with the control group, the SGA group had a significantly lower fractional anisotropy in 16 brain regions (P<0.01), a significantly higher mean diffusivity in 7 brain regions (P<0.05), a significantly higher axial diffusivity in 8 brain regions (P<0.05), and a significantly higher radial diffusivity in 16 brain regions (P<0.05).</p><p><b>CONCLUSIONS</b>FGR may cause abnormalities in the maturity and integrity of white matter fiber tracts.</p>

[Effects of traditional Tibetan drug Liu Tea on proliferation and chemotherapeutic sensitivity of drug-resistant human gastric cancer cell BGC823/5-FU].

To investigate the effects of Liu Tea extracts(LTE) on proliferation, apoptosis and drug sensitivity of drug-resistant gastric cancer cell BGC823/5-FU. MTT assay was used to analyze effect of LTE on cell growth and sensitivity chemotherapeutic drugs, and synergistic effect of the combination of LTE with 5-FU on BGC823/5-FU cells. Combination index (CI) was calculated by CompuSyn. Cell apoptosis was measured by flow cytometry (FCM). Protein expressions of P-gp, Bcl-2, Bax and Caspase-3 (17KD) were detected by Western blot at different concentrations of LTE in BGC823/5-FU cells (100, 200, 400 mg•L⁻¹). The results showed that LTE had an inhibitory effect on growth of BGC823/5-FU cell in a dose-time-dependent manner and significantly reduced IC50 of 5-FU, CDDP, PTX and ADM to BGC823/5-FU cells(P<0.05), indicating it could reverse tolerance of drug resistant cells to chemotherapeutic drugs, with reversion multiples of 2.35, 1.68, 1.96, 0.52. The combination of LTE with 5-FU had positive synergistic effect on the BGC-823 cell line. FCM assay suggested that LTE could induce BGC823/5-FU apoptosis. The apoptosis rate was up to 46.2% when the cells were treated with 800 mg•L⁻¹ LTE after 24 h(P<0.01). According to the protein detection results, with the increase in concentration of LTE, the protein expression of Bcl-2 was gradually decreased(P<0.01), the expression of Bax and Caspase-3 were extremely increased(P<0.01), with statistical significance in difference(P<0.01) but no difference in the expression of P-gp between experiment group and control group. LTE can inhibit the growth of drug-resistant human gastric cancer cell BGC823/5-FU and reverse its chemotherapeutic tolerance to some extent. Inhibition of antiapoptotic proteins, activation of proapoptotic proteins and induction of apoptosis of resistant cells may be its main mechanisms.

Effects of traditional Tibetan drug Liu Tea on proliferation and chemotherapeutic sensitivity of drug-resistant human gastric cancer cell BGC823/5-FU / 中国中药杂志

To investigate the effects of Liu Tea extracts(LTE) on proliferation, apoptosis and drug sensitivity of drug-resistant gastric cancer cell BGC823/5-FU. MTT assay was used to analyze effect of LTE on cell growth and sensitivity chemotherapeutic drugs, and synergistic effect of the combination of LTE with 5-FU on BGC823/5-FU cells. Combination index (CI) was calculated by CompuSyn. Cell apoptosis was measured by flow cytometry (FCM). Protein expressions of P-gp, Bcl-2, Bax and Caspase-3 (17KD) were detected by Western blot at different concentrations of LTE in BGC823/5-FU cells (100, 200, 400 mg•L⁻¹). The results showed that LTE had an inhibitory effect on growth of BGC823/5-FU cell in a dose-time-dependent manner and significantly reduced IC₅₀ of 5-FU, CDDP, PTX and ADM to BGC823/5-FU cells(P<0.05), indicating it could reverse tolerance of drug resistant cells to chemotherapeutic drugs, with reversion multiples of 2.35, 1.68, 1.96, 0.52. The combination of LTE with 5-FU had positive synergistic effect on the BGC-823 cell line. FCM assay suggested that LTE could induce BGC823/5-FU apoptosis. The apoptosis rate was up to 46.2% when the cells were treated with 800 mg•L⁻¹ LTE after 24 h(P<0.01). According to the protein detection results, with the increase in concentration of LTE, the protein expression of Bcl-2 was gradually decreased(P<0.01), the expression of Bax and Caspase-3 were extremely increased(P<0.01), with statistical significance in difference(P<0.01) but no difference in the expression of P-gp between experiment group and control group. LTE can inhibit the growth of drug-resistant human gastric cancer cell BGC823/5-FU and reverse its chemotherapeutic tolerance to some extent. Inhibition of antiapoptotic proteins, activation of proapoptotic proteins and induction of apoptosis of resistant cells may be its main mechanisms.

[Study on Precursors for Synthesis of Anthraquinone Metabolites from Rheum tanguticum].

OBJECTIVE: To explore the potential precursors of the anthraquinone metabolites from Rheum tanguticum and preliminanly identify the synthesis pathway thereof. METHODS: Sterile seedlings sprouted from the seeds of Rheum tanguticum were chosen as materials for inducing callus. The effects of different precursors and feeding duration on the callus of Rheum tanguticum and the anthraquinone yield in adult rheum were studied. RESULTS: The greatest improvement of anthraquinone yield was achieved by acetic acid, increasing 43. 9% for the callus and 45. 8% in the adult rheum; the second greatest improvement was achieved by malonic acid, increasing 15. 8% for the callus and only 3. 6% in the adult rheum. The yield of anthraquinone was not influenced significantly by benzoic acid and p-benzoquinone, and in contrast, was inhibited in some degree by shikimic acid and α-ketoglutaric acid. A suitable feeding duration was 36 h, which worked well for the effects of precursors. CONCLUSION: The precursor for synthesis of anthraquinone metabolites from Rheum tan- guticum is acetic acid, which improves the yields of callus and anthraquinone in adult rheum, concluding that the anthraquinone metabolites are synthesized via polyketone pathway.